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Common carrier material for targeting anticancer drug and gene and preparation and application

An anti-tumor drug and carrier material technology, applied in the field of targeted anti-tumor drugs and gene co-carrying carrier materials, can solve problems such as multi-drug resistance and side effects, achieve reduced toxic side effects, high stability, and avoid mass release Effect

Inactive Publication Date: 2013-03-06
TIANJIN MEDICAL UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0008] The purpose of the present invention is to provide a graphene oxide-based targeted anti-tumor drug and gene co-carrier material and its preparation and application, which is aimed at solving the problem that chemotherapy drugs have great side effects on normal human tissues and are prone to multi-drug resistance. Combining anti-tumor drugs and gene molecules for targeted delivery, so that the two can achieve a sequential combined effect at the micro level, improve their respective anti-tumor efficacy, and reduce the drug’s effect on normal organs and tissues of the human body. toxic side effect

Method used

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  • Common carrier material for targeting anticancer drug and gene and preparation and application
  • Common carrier material for targeting anticancer drug and gene and preparation and application
  • Common carrier material for targeting anticancer drug and gene and preparation and application

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Effect test

Embodiment 1

[0046] The first step: synthesis of graphene oxide material, the preparation process can refer to (ACSNano, 2008, 2,463-470); the core of this step is to obtain graphene oxide material. Similarly, other methods can also be used to obtain graphene oxide materials.

[0047] Step 2: Preparation of lactose acylated chitosan:

[0048] Lactobionic acid 0.2671 g, 1-ethyl-3(3-dimethy amino-propyl) carbodiimide (EDC) 0.1715 g, N-hydroxy succinimide (NHS) 0.1030 g dissolved in 5 mL of distilled water, dissolved by ultrasound, activated by electromagnetic stirring for 1 hour . Weigh 1 g of purified chitosan, dissolve it in 3 mL of distilled water, dissolve it by ultrasound, mix it with activated lactobionic acid, add triethylamine to adjust the pH to 8-9, and react with electromagnetic stirring for 48 hours. The system is revolved to remove the solvent, the concentrate is passed through a dextran gel column, the yellow solution that flows out is collected, and the product is concentrated an...

Embodiment 2

[0066] The first step: synthesis of graphene oxide material, the preparation process can refer to (ACSNano, 2008, 2,463-470); the core of this step is to obtain graphene oxide material. Similarly, other methods can also be used to obtain graphene oxide materials.

[0067] Step 2: Preparation of folic acid and chitosan conjugate:

[0068] 109.4 mg of folic acid, 95.85 mg of 1-ethyl-3(3-dimethy amino-propyl) carbodiimide (EDC), and 57.5 mg of N-hydroxy succinimide (NHS) were dissolved in 10 mL DMSO. After dissolution by ultrasound, it was activated by electromagnetic stirring for 1 hour. Weigh 500 mg of purified chitosan, dissolve it by ultrasound, add 200 μL of triethylamine, and react with electromagnetic stirring at 30-40 ℃ for 72 hours. The system was revolved to remove the solvent, 80 mL of acetone was added for precipitation, and the precipitate was washed twice with acetone. The precipitate was dissolved in water, centrifuged for 5 minutes (1000 rpm), and the supernatant was...

Embodiment 3

[0085] The first step: synthesis of graphene oxide material, the preparation process can refer to (ACSNano, 2008, 2,463-470); the core of this step is to obtain graphene oxide material. Similarly, other methods can also be used to obtain graphene oxide materials.

[0086] Step 2: Preparation of folic acid and chitosan conjugate:

[0087] 109.4 mg of folic acid, 95.85 mg of 1-ethyl-3(3-dimethy amino-propyl) carbodiimide (EDC), and 57.5 mg of N-hydroxy succinimide (NHS) were dissolved in 10 mL DMSO. After dissolution by ultrasound, it was activated by electromagnetic stirring for 1 hour. Weigh 400 mg of purified chitosan, dissolve it by ultrasound, add 200 μL of triethylamine, and react with electromagnetic stirring at 30-40 ℃ for 72 hours. The system was revolved to remove the solvent, 80 mL of acetone was added for precipitation, and the precipitate was washed twice with acetone. The precipitate was dissolved in water, centrifuged for 5 minutes (1000 rpm), and the supernatant was...

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Abstract

The invention relates to a common carrier material based on graphene oxide for a targeting anticancer drug and a gene and application and application. Folic acid, lactobionic acid and other tumor cell targeting or liver targeting molecules and part of amino groups of soluble chitosan are connected by amide bonds to prepare a conjugate, the conjugate is then connected with graphene oxide, quaternization is performed by using an epoxy compound with a quaternary ammonium group, and gene molecules are loaded by the quaternizationquaternized part of the chitosan through electrostatic attraction; and then the anticancer drug is loaded by pi-pi conjugates, hydrogen bonds and hydrophobic effects in a non-covalent bond method. By adopting the targeting performance of targeting molecules and effects of graphene oxide of a particular size to enhance penetration and retention in tumor tissues and combining the performance of the graphene oxide for pH response control release of the loaded drug, the drug can be realized released in a tumor cell, an intelligent delivery system for the common carrier of the tumor targeting or liver targeting anticancer drug and the gene is synthesized from the perspective of synergetic medication, and a theoretical basis and a method basis are provided for combined therapy of tumor.

Description

technical field [0001] The present invention relates to a targeted anti-tumor drug and gene co-loading carrier material and its preparation and application, specifically to a functionalized graphene oxide-based targeted anti-tumor drug and gene and other negatively charged biomolecule co-loading carrier Materials and their preparation methods and applications. Background technique [0002] Combining genes and anti-tumor drugs for targeted delivery can simulate the combined drug mode of clinical tumor treatment, and through synergistic effects through different channels, the two can achieve sequential combined effects at the microscopic level, improving their respective anti-tumor effects. Tumor curative effect, while reducing the toxic and side effects of drugs on normal organs and tissues of the human body. For example, multidrug resistance is the main reason why many cancer chemotherapy is ineffective or gradually ineffective. If antitumor drugs and small interfering RNA...

Claims

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Application Information

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IPC IPC(8): A61K47/02A61K47/36A61K47/42A61K48/00A61P35/00
Inventor 杨晓英曹秀芬王银松段宏泉陈永胜
Owner TIANJIN MEDICAL UNIV
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